Treatment of Breast Cancer in SCID Mice with Regulatory Suicide Gene
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Abstract:
Objective:To explore the ganciclovir(GCV) therapy on the severe combined immunodeficiency (SCID) breast cancer mice after HSVtk gene and Tet-On regulatory gene expression induced by doxycycline(Dox). Methods:Co-transfections of pRevTRE/HSVtk and pRevTet-On were performed on MCF-7 cell line by using modified calcium phosphate precipitattion method respectively. After MCF/TRE/tk/Tet-On cell line was established,cells were inoculated into the SCID mice to form the human breast cancer in SCID mice. Regimen (GCV, GCV+DOX, Normal Saline) was injected introperitoneally in SCID mice 15 days. The volume of tumor was measured and the tumor tissues were examined pathologically. HSVtk gene expression was analyzed by RT-PCR. Results:The human breast cancer in SCID mice was formed successfully by inoculated MCF/TRE/tk/Tet-On cells into the female SCID mice. In the GCV+DOX-treated group, volume of tumors was shrank remarkably after 15 days' treatment and tumor growth were retarded compared with the control groups. There was significant difference between the GCV+DOX-treated group and the control groups (P<0.05). Infiltrating cells were observed in tumors that injected with doxycycline followed by GCV treatment and cells were profoundly damaged stained with hematoxylin and eosin. The expression of tk gene in SCID mice tumors was also obeserved by RT-PCR analysis.Conclusions:The human breast cancer in SCID mice was formed successfully by implanted MCF/TRE/tk/Tet-On cells. The growth of tumor could be shrank remarkably with GCV treatment in our SCID mice under the doxycycline induction.